A permeation enhancer for increasing transport of therapeutic macromolecules across the intestine

Gupta, Vivek; Hwang, Byeong Hee; Doshi, Nishit; Mitragotri, Samir

doi:10.1016/j.jconrel.2013.05.002

Cited by 65 publications

(35 citation statements)

References 62 publications

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“…Another absorption enhancer is tetradecylmaltoside, which also enhances the uptake of low-molecular-weight heparin 119 . The screening of a large library of chemicals and chemical mixtures to identify compositions that enhance the uptake of peptides and proteins 120 led to the identification of the zwitterionic surfactant dimethyl palmitoyl ammonio propanesulphonate (PPS), which enhanced the intestinal permeation of calcitonin in mice 121 . Other methods of increasing absorption include pH-sensitive hydrogels to protect the drug from low pH in the stomach 122 , chitosans 123 and chitosan derivatives 124 to induce mucoadhesion of the drug carrier and increase intestinal permeation, and acrylate-based polymers to increase mucoadhesion 125 .…”

Section: Alternative Routes Of Drug Deliverymentioning

confidence: 99%

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Mitragotri

Burke

Langer

2014

Nat Rev Drug Discov

Self Cite

1,336

1,037

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The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies — such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs — and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.

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Section: Alternative Routes Of Drug Deliverymentioning

confidence: 99%

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Mitragotri

Burke

Langer

2014

Nat Rev Drug Discov

Self Cite

1,336

1,037

View full text Add to dashboard Cite

show abstract

“…The strategies used to optimize protein and peptide delivery focus on two main goals: tissue wall localization and enhanced permeation. Chemical modification strategies including mutagenesis, proteinylation, glycosylation, PEGylation and prodrugs as well as formulation strategies based on the use of absorption enhancers like nanoparticles, microspheres, liposomes and emulsions, have been used to increase the bioavailability to between 1–2% [13–21]. This threshold allowed for the development of oral vaccines using hydrogel-carriers and nanoparticle-based techniques to protect the antigen from the hostile environment of the GI tract [20,22–24].…”

Section: Introductionmentioning

confidence: 99%

Oral delivery of biologics using drug-device combinations

Caffarel–Salvador

Abramson

Langer

et al. 2017

Current Opinion in Pharmacology

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Orally administered devices could enable the systemic uptake of biologic therapeutics by engineering around the physiological barriers present in the gastrointestinal (GI) tract. Such devices aim to shield cargo from degradative enzymes and increase the diffusion rate of medication through the GI mucosa. In order to achieve clinical relevance, these designs must significantly increase systemic drug bioavailability, deliver a clinically relevant dose and remain safe when taken frequently. Such an achievement stands to reduce our dependence on needle injections, potentially increasing patient adherence and reducing needle-associated complications. Here we discuss the physical and chemical constraints imposed by the gastrointestinal organs and use these to develop a set of boundary conditions on oral device designs for the delivery of macromolecules. We critically examine how device size affects the rate of intestinal obstruction and hinders the loading capacity of poorly soluble protein drugs. We then discuss how current orally administered devices could solve the problem of tissue permeation and conclude that these physical methods stand to provide an efficacious alternative to the classic hypodermic needle.

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“…To improve bioavailability of these drugs by oral administration, various promising strategies have been utilized to circumvent these obstacles (Renukuntla et al, 2013). These strategies include using enzyme inhibitors (Bernkop-Schnurch, 1998;Su et al, 2012) and drug delivery systems (Mahato et al, 2003;Fan et al, 2014) to protect these drugs from enzymatic degradation, as well as chemical absorption enhancers (Gupta et al, 2013) directing at improving intestinal epithelium membrane permeability. However, many of these approaches have been achieved limited success due to their drawbacks inherently.…”

Section: Introductionmentioning

confidence: 99%

Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec)

et al. 2015

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Biodegradable polymer nanoparticle drug carriers are an attractive strategy for oral delivery of peptide and protein drugs. However, their ability to cross the intestinal epithelium membrane is largely limited. Therefore, in the present study, cell-penetrating peptides (R8, Tat, penetratin) and a secretion peptide (Sec) with N-terminal stearylation were introduced to modify nanoparticles (NPs) on the surface to improve oral bioavailability of peptide and protein drugs. In vitro studies conducted in Caco-2 cells showed the value of the apparent permeability coefficient (Papp) of the nanoparticles co-modified with Sec and penetratin (Sec-Pen-NPs) was about two-times greater than that of the nanoparticles modified with only penetratin (Pen-NPs), while the increase of transcellular transport of nanoparticles modified together with Sec and R8 (Sec-R8-NPs), or Sec and Tat (Sec-Tat-NPs), was not significant compared with nanoparticles modified with only R8 (R8-NPs) or Tat (Tat-NPs). Using insulin as the model drug, in vivo studies performed on rats indicated that compared to Pen-NPs, the relative bioavailability of insulin for Sec-Pen-NPs was 1.71-times increased after ileal segments administration, and stronger hypoglycemic effects was also observed. Therefore, the nanoparticles co-modified with penetratin and Sec could act as attractive carriers for oral delivery of insulin.

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A permeation enhancer for increasing transport of therapeutic macromolecules across the intestine

Cited by 65 publications

References 62 publications

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Oral delivery of biologics using drug-device combinations

Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec)

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